tbuckley/cabot-search huggingface dataset:
A phase II trial of paclitaxel plus biweekly cetuximab for patients with recurrent or metastatic head and neck cancer previously treated with both platinum-based chemotherapy and anti-PD-1 antibody.
Authors: Taiji Koyama, Naomi Kiyota, Yoshinori Imamura, Shogen Boku, Nobuhiro Shibata, Hironaga Satake, Kaoru Tanaka, Hidetoshi Hayashi, Shigemichi Iwae, Takuma Onoe, Yukinori Asada, Tomoko Yamazaki, Taku Nose, Shinya Ohata, Shiro Kimbara, Yoshiaki Nagatani, Hironobu Minami
Journal: Journal of Clinical Oncology (2023)

6032 Background: An important unmet need in treatment options remains for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC) previously treated with both platinum-based chemotherapy and anti-PD-1 antibody (PD-1 Ab). Recent retrospective studies suggest that previous treatment with Immune checkpoint inhibitor might augment the efficacy of subsequent chemotherapy. This phase II trial aimed to evaluate the efficacy and safety of paclitaxel plus biweekly cetuximab (PTX+bwCmab) for patients with R/M-HNSCC previously treated with both platinum and PD-1 Ab. Methods: This is a single-arm, multicenter phase II trial. Key eligibility criteria were R/M-HNSCC; previous treatment with both platinum-based chemotherapy and PD-1 Ab; ECOG performance status 0 or 1; measurable disease per RECIST v1.1; and adequate organ function. PTX+bwCmab consisted of weekly paclitaxel 100 mg/m 2 (days 1, 8, 15) and biweekly cetuximab 500 mg/m 2 (days 1, 15) with a cycle of 28 days. Primary endpoint was objective response rate (ORR). We set a null hypothesis of 10% and alternative of 30% with a one-sided alfa of 0.05 and power of 90%. Secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events (AEs) (CTCAE v5.0). Binominal confidence intervals (CIs) for ORR and DCR were estimated by the exact method. Time-to-event analyses were calculated by the Kaplan-Meier method with 95% CIs. Results: Between August 2020 and August 2022, 35 patients were enrolled, of whom 32 were evaluable for response. ORR was 68.7% (95% CI: 49.9-83.8), which met the prespecified criteria for the primary endpoint of ORR. With a median follow-up period for survivors of 16.6 months, median PFS and OS were 5.7 and 13.4 months, respectively. DCR was 93.7% (95% CI: 79.1-99.2). The most common AEs of any grade were skin rash (65%), peripheral nerve neuropathy (45%), neutropenia (40%), fatigue (40%) and paronychia (37%). Grade 3 and 4 adverse events included neutropenia (34%), mucositis (8%), pneumonitis (8%) and febrile neutropenia (5%). These AEs were manageable and no treatment-related death within 30 days was observed. Conclusions: PTX+bwCmab showed highly encouraging efficacy and tolerability in RM-HNSCC patients previously treated with both platinum and PD-1 Ab. Although preliminary, these results suggest that this is a promising treatment option for this hitherto untreatable patient group. Further evaluation is warranted. Clinical trial information: jRCTs051200040 .
18F-FDG PET/CT parameters in precision treatment planning for locally advanced squamous cell carcinoma of the uterine cervix.
Authors: Chyong-Huey Lai, Feng-yuan Liu, Wei-Chun Chen, Lan-Yan Yang, Chun-Chieh Wang, Angel Chao
Journal: Journal of Clinical Oncology (2023)

e17508 Background: Concurrent chemoradiotherapy (CCRT) is the standard of care for locally advanced cervical cancer. We aimed to analyze pretreatment 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) parameters and clinicopathological characteristics in patients with locally advanced cervical squamous cell carcinoma (SCC) to establish a scoring system for prognostic stratification. Methods: Cohort 1 consisted of patients with cervical SCC with FIGO (2009) stage III-IVA or stage I-II with positive nodes on PET/CT recruited in AGOG09-001 trial. Cohort 2 consisted of institutional patients treated in 2016-2020 with similar inclusion criteria. Pretreatment clinical characteristics and PET/CT parameters including maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) of cervical tumor and nodal SUVmax were assessed for outcomes using the stepwise multivariable Cox regression. Results: With two cohorts combined (Cohort 1, n= 55, Cohort 2, n= 120), the median follow-up for 175 patients was 55 months (range, 2-164). Age (≥66 years old), MTV (≥87.1 mL) of cervical tumor and PET/CT-defined para-aortic lymph node (PALN) metastasis were independent significant adverse predictors for cancer-specific survival (CSS) ( P&lt;0.001, P=0.002, and P=0.033, respectively). Counting each risk predictor as score one, patients with risk score sum 0, 1, 2, 3 had a 5-year CSS of 85.8%, 68.5%, 29.7%, and 0%, respectively ( P&lt;0.001). Conclusions: Age, cervical tumor MTV and PET/CT-defined PALN metastasis are independent risk predictors in locally advanced cervical SCC. Patients with risk score sum 0 may receive CCRT with single-agent cisplatin, while patients with risk score sum ≥1 may consider receiving novel combination therapies or entering clinical trials.
Bone health practices in metastatic prostate cancer (mPCA).
Authors: Corbin Jeffrey Eule, Junxiao Hu, Danielle Gilbert, Joy Eskandar, Elaine T. Lam
Journal: Journal of Clinical Oncology (2023)

e17119 Background: Patients (pts) with mPCA and bone metastases (BM) are at risk for skeletal-related events (SREs), which include pathologic fracture, bone irradiation or surgery, spinal cord compression, and hypercalcemia. This study examined the evaluation, prevention, and treatment of osteopenia/-porosis (OP/P) and BM in pts with mPCA at the UCCC and affiliated sites. Methods: Pts diagnosed with mPCA and BM between 2011-2021 and treated with ADT were included. Demographic, clinical, treatment, and outcomes data were retrospectively collected. The primary endpoint was time from mPCA diagnosis to first SRE. Secondary endpoints included rates of DEXA scans, rates of vitamin D and calcium supplementation, and bone agent toxicity. The log-rank test was conducted to compare the primary endpoint by use of a bone strengthening agent. The Kruskal Wallis non-parametric test was used for continuous variables and Fisher’s exact test for categorical variables. Results: Of the 369 pts with mPCA, 247 (66.9%) were treated with a bone agent. Median age at metastatic diagnosis (mDx) was 69.6 years. Pts were predominately white (315, 85.4%) with hormone-sensitive mPCA (mHSPC) (327, 88.6%) at mDx. There were no significant differences in race, ethnicity, PSA, Gleason score, or time on ADT between patients who did and did not receive a bone agent. 222 pts (60.2%) were former or current smokers, 5 (1.4%) had pre-existing low testosterone ( &lt; 150 ng/dL), 8 (2.2%) had prolonged glucocorticoid use (equivalent &gt; 10 mg prednisone for 30 days), and 17 (4.6%) had known OP/P prior to mDx. 130 pts (35.3%) had a DEXA scan (27 pre-ADT, 103 post-ADT). 325 pts (88.1%) and 286 pts (77.5%) were recommended vitamin D and calcium supplementation, respectively. Bone agent use and toxicity are presented in table 1. 110 of 247 pts (44.5%) treated with a bone agent were started in the mHSPC setting without OP/P. Time from mPCA diagnosis to first SRE was a median of 32.8 months (IQR 13.5 to 66.8) for pts who received a bone agent vs. 28.2 months (IQR 8.7 to 59.1) who did not (Chi-squared = 7.089, p = 0.008). Among SREs, 102 pts (27.6%) had a pathologic fracture, 1 (0.3%) severe hypercalcemia &gt; 14 mg/dL, 23 (6.2%) bone surgery, 142 (38.5%) bone irradiation, and 4 (1.1%) spinal cord compression. Conclusions: Bone agent use was associated with an expected improvement in time to first SRE. Pts with mPCA had high rates of vitamin D and calcium supplementation for OP/P prevention. Denosumab was the most used bone agent in concordance with guidelines for mPCA. DEXA scan rates were low, and nearly half of patients received a bone agent prior to castrate resistance. [Table: see text]
Camrelizumab combined with lenvatinib and RALOX-HAIC for hepatocellular carcinoma (HCC) in BCLC stage B and C: A prospective, single-arm, phase II trial (Cal Era study).
Authors: Jinzhang Chen, Mengya Zang, Huajin Pang, Chuanjiang Li, Jianbo Zhao, Yabing Guo, Jinlin Hou
Journal: Journal of Clinical Oncology (2023)

e16128 Background: The combination of systemic therapies and hepatic arterial infusion chemotherapy (HAIC) showed promising outcomes for advanced hepatocellular carcinoma (HCC). Raltitrexed, an antimetabolic drug with long plasma concentrations half-life, could be used in short infusions. HAIC with raltitrexed plus oxaliplatin (RALOX) was reported to be effective and safe in HCC. This study aimed to investigate the efficacy and safety of combined camrelizumab and lenvatinib plus RALOX-HAIC as a first-line treatment in advanced HCC patients. Methods: This single-arm, phase II study included treatment-naive adult (≥18 years) patients with HCC in BCLC stage B and C and Child-Pugh score small or equal to 7 points (NCT05003700). Patients were administrated with RALOX-HAIC (oxaliplatin 100mg/m 2 , raltitrexed 3 mg/m 2 , every 3 weeks), combined with camrelizumab (200mg by IV infusion, every 3 weeks) and lenvatinib (8mg orally once daily) for 6 cycles, followed by maintenance therapy with camrelizumab and lenvatinib until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Results: Between March 2021 and October 2022, 36 patients (33 men and 3 women; median age, 54.5 years) were enrolled. The median tumor size was 11.4 cm, 86.1% of patients had portal vein invasion, and 38.9% had extrahepatic metastasis. As of February 1, 2023, the median follow-up was 14.2 months, and all patients had at least one post-baseline tumor assessment. The confirmed ORR per RECIST v1.1 and per mRECIST was respectively 61.1% (95% CI, 44.4−77.8), and 83.3% (95% CI, 70.5−96.1) including 4(11.1%) patients who achieved a complete radiological response. The median progression-free survival (PFS) time was 13.8 months (95%CI, 8.8-20.5) per RECIST v1.1. The 6-month and 12-month overall survival rate were 94.3% and 64.9%, respectively. Grade 3-4 treatment-related adverse events (AEs) occurred in 75% of patients, and the most common were neutropenia (44.4%) thrombocytopenia (36.1%), elevated aspartate aminotransferase (25.0%), and leucopenia (19.4%). All AEs were expected and manageable, and no treatment-related deaths were reported. Conclusions: Combination treatment with camrelizumab and lenvatinib plus RALOX-HAIC showed promising antitumor activity and acceptable toxicity in patients with advanced HCC. Clinical trial information: NCT05003700 .
Circulating levels of PCSK9, ANGPTL3, and other lipid-related factors in men with high-grade prostate cancer.
Authors: France-Hélène Joncas, Ann-Charlotte Bergeron, Emilie Yan Pin Wong Chong, Karine Robitaille, Vincent Fradet, Alain Bergeron, Frédéric Calon, Nabil Georges Seidah, Anne Gangloff
Journal: Journal of Clinical Oncology (2023)

e17001 Background: Cancer cells rely on abundant lipid supplies for growth and metastasis. Previous studies have shown that lipid-lowering drugs provide a protective effect against cancer progression, including prostate cancer. However, the role of hyperlipidemic factors has not yet been extensively studied. Here, we aimed to measure circulating levels of hyperlipidemic factors, such as PCSK9 and ANGPTL3, in a small cohort of men diagnosed with high-grade prostate cancer compared to men without cancer. Methods: Plasma samples and data were obtained from 70 consenting men treated at CHU de Québec-Université Laval. Thirty-five patients with high-grade prostate cancer (cases) were age and BMI-matched to 35 patients without cancer (controls). The circulating levels of various lipids, Apo B and Lp(a) were obtained with a Roche Modular analytical platform, whereas levels of PCSK9, ANGPTL3 and leptin were measured by ELISA. We performed group comparisons and correlations using R version 4.2.1. Results: As expected, Prostate-specific antigen (PSA) levels were significantly higher in the cancer group. The lipid profile as well as Lp(a) and leptin levels did not differ between groups. ANGPTL3 level tended to be lower in patients with prostate cancer without reaching statistical significance (mean 32.2 vs 36.3 ng/mL, p = 0.051). ANGPTL3 level also inversely correlated with leptin among the cases (rho = -0.44, p = 0.008). PCSK9 level was similar in both groups, but inversely correlated with PSA in the cancer group (rho = -0.39, p = 0.022). PSA level correlated with triglycerides, total cholesterol, Apo B, non-HDL-cholesterol and LDL in the control group (p &lt; 0.05). Conclusions: None of the hyperlipidemic factors measured here was significantly different between high-grade prostate cancer patients and controls. However, the trend for lower ANGPTL3 levels in cancer, as well as the inverse correlations between PCSK9 and PSA and between ANGPTL3 and leptin levels in cancer patients, warrant further investigation in larger cohorts.
Real-world evidence analysis of early-stage prostate cancer using natural language processing.
Authors: Álvaro Juárez, Joan Carles, Antonio José Conde-Moreno, Pablo Maroto-Rey, Javier Puente, Jacobo Muñoz Del Toro, Jose M Calderon, Maria Lopez, Juan Valdivieso, David Casadevall, Miren Taberna, Antonio Alcaraz
Journal: Journal of Clinical Oncology (2023)

e17007 Background: Real-world evidence (RWE) on the epidemiology and management of localized/locally advanced prostate cancer (LPC) is lacking. Here we used EHRead, a natural language processing framework based on SNOMED CT terminology, to extract clinical information from electronic health records (EHRs) to perform a comprehensive description of a real-world cohort of LPC patients. Here we present a follow-up of the project already communicated at ESMO 2020. Methods: This is an observational, multicenter, retrospective study based on the secondary analysis of free-text and structured clinical information found in EHRs from all observed adult patients with LPC between January 2014 and December 2018 in 12 Spanish hospitals. A total of 375 variables were extracted using EHRead to assess patient clinical characteristics, treatment patterns and journey across different prostate cancer stages. Event-free survival (EFS) was analyzed in incident LPC patients with presence of Gleason or PSA and follow-up greater than 0 days. A multivariable Cox-proportional hazards model was applied to obtain adjusted hazard ratios (aHR). Results: We observed 19788 patients with LPC during a median of 3.5 (interquartile range 1.4-7.4) years of follow-up. 52% of patients had low- (LR), 21% intermediate- (IR) and 27% high-risk (HR) disease. 3938 (18%) patients transitioned to other disease stages, leading to castration-resistant prostate cancer (mCRPC) in 4%, 7%, 16% of patients with LR, IR, and HR LPC, respectively. 7884 (42%) patients received radiotherapy (RT), 7021 (38%) prostatectomy (PT), 6061 (31%) androgen deprivation therapy (ADT), and 1034 (6%) active surveillance. Local recurrence was observed in 3% and distant metastasis in 11% (57% bone, 37% visceral). Distant metastases were observed in 7%, 12% and 21% of HR, IR and LR; 8% vs. 9% of PT vs. RT; and 16% vs 6% of ADT vs. no ADT, respectively. EFS was assessed in 7465 (38%) patients, with a 4-year EFS rate of 18%. Median EFS was 22, 13, and 8 months for LR, IR, HR; 23 vs. 12 months for PT vs. RT; and 8 vs. 21 months for ADT vs. no ADT, respectively. A multivariable cox proportional hazards model is presented in the following Table. Conclusions: During the study period, 11% of all LPC patients developed metastatic disease, with only 18% remaining event-free at 4 years. Transition to mCRPC was 4- and 2-fold higher in HR vs. IR and LR disease, respectively. Disease risk, treatment with RT and/or addition of ADT were independently associated with shorter EFS. Our findings suggest that, despite adjuvant treatment, LPC local extension and histopathological characteristics at diagnosis remain critical determinants of patient prognosis. A more detailed analysis in patients with available Gleason and PSA is underway. [Table: see text]
Utility of circulating tumor DNA for identifying genetic mutations in cholangiocarcinoma of East Asian patients.
Authors: Cheng Liu, Yiming Fu, Zebin Xiao, Yaru Chen, Defeng Dai, Shaochen Cheng, Xiang Li
Journal: Journal of Clinical Oncology (2023)

e16332 Background: Cholangiocarcinoma, also referred to as bile duct cancer, is a major global health concern. The diagnosis of this cancer is often difficult due to its lack of distinctive symptoms and its tendency to present at advanced stages. However, the recent emergence of blood liquid biopsy as a diagnostic tool has shown great potential for detecting and managing cholangiocarcinoma. The use of blood liquid biopsy in East Asian populations, where the incidence of cholangiocarcinoma is particularly high, has the potential to improve the accuracy of diagnosis, prognosis, and targeted treatment planning. Methods: The study cohort contains 53 Chinese cholangiocarcinoma patients, the examination of DNA from tumor tissue (tDNA), blood (cfDNA), and blood leukocytes (gDNA) was performed using 680 gene targeted capture sequencing and analyzing for CNV, fusion, SNV, indel, MSI, and TMB. The sequencing depth was 2200X for tDNA, 20000X for bDNA, and 10000X for gDNA. In the tissue samples evidence of PD-L1 expression was examined. The TMB was classified as high (TMB-H) with a cutoff &gt; 10 mutations/megabase and low (TMB-L) &lt; 10. Microsatellite instability-high (MSI-H) was identified in cases where instability was observed &gt; 20% of 117 loci, and the microsatellite stable (MSS) rate was determined to be &lt; 20%. Results: In a cohort of 53 patients, a thorough analysis of tissue and blood samples was conducted to detect somatic mutations. 146 (38.1%) shared mutations were found in both tDNA and cfDNA, while 211 (55.09%) and 25 (6.53%) unique mutations were found in tDNA and cfDNA respectively. Of the 64 mutations found in CNV, 5 (7.81%) were shared in tDNA and cfDNA, 52 (81.25%) were unique in tissues, and 7 (10.93%) were unique in blood. High frequency mutated genes were also revealed as TP53, KRAS, SMAD4, LRP1B, and ARID1A, which were consistent with the results from the IntoGen database (4 cohorts, 393 samples). Notably, LRP1B (11.32%, 6/53) was not detected in the validation cohort. 96.23% of the samples showed consistent tTMB vs. bTMB outcomes, with only 1 sample exhibiting high PD-L1 expression and TMB-L, MSS, and 1 sample (out of 52 with MSS) having TMB-H and PD-L1 expression less than 1%. Conclusions: The results of the mutation analysis suggest that relying solely on cfDNA for molecular typing of cholangiocarcinoma is not sufficient. This highlights the importance of testing tissue samples in order to accurately detect tumor mutations in cholangiocarcinoma. Further research is needed to determine the significance of LRP1B, a gene that was frequently mutated in the study cohort but not found in the validation cohort, in the diagnosis and treatment of cholangiocarcinoma.
Adjuvant chemotherapy in ypStage III locally advanced rectal cancer after neoadjuvant treatment with an oxaliplatin-based regimen.
Authors: Runkai Cai, Jianwei Zhang, Yue Cai, Zehua Wu, Huabin Hu, Xiaoyu Xie, Yanhong Deng, Yi Cheng, Yuting Zhang
Journal: Journal of Clinical Oncology (2023)

e15628 Background: Fluorouracil -based neoadjuvant chemoradiotherapy(CRT) followed by total mesorectal excision and adjuvant chemotherapy is the standard treatment for locally advanced rectal cancer (LARC). Adjvuant FOLFOX improved survival benefit compared with fluorouracil in patients with ypStage II andIII after CRT. However, induction or consolidation chemotherapy with FOLFOX before surgery had been the new standard for LARC. Whether adjuvant chemotherapy with FOLFOX still improves survival outcomes in ypStage III patients previously exposed to oxaliplatin-based treatment was unknwon. Methods: Patients with LARC receiving oxaliplatin-based neoadjuvant treatment from January 2015 to December 2019 were retrospective analyzed. The inclusion criteria included neoadjuvant FOLFOX chemotherapy alone or induction chemotherpay, concurrent FOLFOX and consolidation chemotherapy before CRT. The duration of neoadjuvant oxaliplatin exposure time was less than 4 months. The efficacy of adjvuant FOLFOX chemotherapy was analyzed among these ypStage III patients according to adjuvant chemotherapy cycles after surgery. Results: A total of 227 patients with ypStage III were enrolled, with the 3-year DFS rate of 46.1% (95%Cl 37.3%-54.9%).Among these patients, 193 patients received adjuvant FOLFOX chemotherapy, including 7 patients had ≤ 2 cycles of adjuvant treatment. And 34 patients had observation after surgery. The 3-year DFS rates bewteen FOXFOL adjvuant chemotherapy group and observation group were 44.7% vs. 56.5%, respectively (HR, 1.190, 95%Cl 0.6246-2.267, P = 0.597). Forty-one patients had ≤ 2 cycles of adjuvant treatment. The 3-year DFS was 43.6% vs. 60.4% (P = 0.597) between pateints receiving over 2 cycles of adjvuant chemotherapy and ≤ 2 cycles of treatment. Conclusions: Among ypStage III LARC pateints after neoadjuvant treatment with Oxaliplatin-Based regimen, adjuvant chemotherapy with FOLFOX failed to improved surival benefit. More enhanced regimen might be necessary for these oxalipatin-resistant patients.